| 1. |
- Ericsson, Olle, et al.
(författare)
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Clinical validation of a novel automated cell-free DNA screening assay for trisomies 21, 13, and 18 in maternal plasma.
- 2019
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Ingår i: Prenatal diagnosis. - : Wiley. - 1097-0223 .- 0197-3851. ; 39:11, s. 1011-1015
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate clinical performance of a new automated cell-free (cf)DNA assay in maternal plasma screening for trisomies 21, 18, and 13, and to determine fetal sex.Maternal plasma samples from 1200 singleton pregnancies were analyzed with a new non-sequencing cfDNA method, which is based on imaging and counting specific chromosome targets. Reference outcomes were determined by either cytogenetic testing, of amniotic fluid or chorionic villi, or clinical examination of neonates.The samples examined included 158 fetal aneuploidies. Sensitivity was 100% (112/112) for trisomy 21, 89% (32/36) for trisomy 18, and 100% (10/10) for trisomy 13. The respective specificities were 100%, 99.5%, and 99.9%. There were five first pass failures (0.4%), all in unaffected pregnancies. Sex classification was performed on 979 of the samples and 99.6% (975/979) provided a concordant result.The new automated cfDNA assay has high sensitivity and specificity for trisomies 21, 18, and 13 and accurate classification of fetal sex, while maintaining a low failure rate. The study demonstrated that cfDNA testing can be simplified and automated to reduce cost and thereby enabling wider population-based screening.
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| 2. |
- Adolfsson, Emma, 1977-, et al.
(författare)
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CNV-Z; a new tool for detecting copy number variation in next generation sequencing data
- 2023
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Ingår i: SoftwareX. - : Elsevier. - 2352-7110. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- We developed an efficient approach to diagnostic copy number analysis of targeted gene panel or whole exome sequence (WES) data. Here we present CNV-Z as a new tool for detection of copy number variants (CNVs). Deletions and duplications of chromosomal regions are widely implicated in both genomic evolution and genetic disorders. However, calling CNVs from targeted or exome sequence data is challenging. In most cases, the copy number of a chromosomal region is estimated as the depth of reads mapping to a certain bin or sliding window divided by the expected number of reads derived from a set of reference samples. This approach will inevitably miss smaller CNVs on an irregular basis, and quite frequently results in a disturbing number of false positive CNVs. We developed an alternative approach to detect CNVs based on deviation from expected read depth per position, instead of region. Cautiously used, the cohort of samples in the same run will do as a reference. With appropriate filtering, given high quality DNA and a set of suitable reference samples, CNV-Z detects CNVs ranging in length from one nucleotide to an entire chromosome, with few false positives. Performance is proved by benchmarking using both in-house targeted gene panel NGS data and a publicly available NGS dataset, both sets with multiplex ligation-dependent amplification probe (MLPA) validated CNVs. The outcome shows that CNV-Z detects single- and multi-exonic CNVs with high specificity and sensitivity using different kind of NGS data. On gene level, CNV-Z shows both excellent sensitivity and specificity. Compared to competing CNV callers, CNV-Z shows higher specificity and positive predictive value for detecting exonic CNVs.
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| 3. |
- Green, Anna, 1973-, et al.
(författare)
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Copy number variants in familial hypercholesterolemia genes using targeted NGS, validated through optical genome mapping
- 2024
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Ingår i: European Journal of Human Genetics. - : Nature Portfolio. - 1018-4813 .- 1476-5438. ; 32:Suppl. 1, s. 159-159
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Objectives: Familial hypercholesterolemia (FH) is a common genetic disorder which is primarily caused by pathogenic variants in the LDLR, APOB, and PCSK9 genes. Approximately 10% of pathogenic variants in LDLR may be CNVs. Here, we combine NGS, MLPA, and Optical Genome Mapping (OGM) to investigate CNVs in LDLR.Methods: A NGS panel was designed for whole gene sequencing (8 genes) of 100 FH patients using Twist technology and Illumina platform. CNVs were detected using CNVexpo, and an in-house pipeline for base-resolved normalized coverage. Identified CNVs were validated using MLPA and OGM. Bionano Services Lab performed the OGM procedure. Purified gDNA was labeled using Direct Label and Stain DNA Labeling Kit. Saphyr chip was run aiming for 100X coverage. De novo assembly and Variant Annotation pipelines were executed on Bionano Solve v3.7. Bionano Access v1.7 was used for CNV reporting and visualization.Results: In five out of 100 samples NGS and MLPA data showed heterozygous deletions in LDLR. Three deletions, affecting different exons, was analyzed and confirmed using OGM. In two samples, OGM better defined the breakpoints as well as the size of the event, which expanded far beyond the gene of interest. In one sample, an additional CNV of SLCO1B1, a pharmaco-gene, important for transport of statins used for FH treatment was identified.Conclusion: CNVs in FH genes in FH patients could be detected using targeted NGS, which was further confirmed by MLPA and characterized using OGM.
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| 4. |
- Jonasson, Anna-Karin
(författare)
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Gränskronotopen och upplösningen av formens värld : En studie av gränstematiken i Kerstin Ekmans trilogi Vargskinnet (1999-2003)
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study is to explore the border theme in the Vargskinnet (The Wolfskin) trilogy (1999–2003) by Kerstin Ekman. Some motifs, such as skin and water, play important roles in this context, as they form part of the novels’ designs of the maintenance, transcending and dissolution of boundaries. These boundary phenomena are derived from different contexts — cultural and geographical, as well as abstract and material — and in the novels they appear mainly as recurring patterns in the novels’ subtext. The trilogy consists of Guds barmhärtighet (God's Mercy), 1999, Sista rompan (The Last String) 2002, and Skraplotter (Lottery Scratchcards), 2003. In addition to the important border motifs, the novels contain, on an overall level, problematisations of the relationship between form and content, between external and internal. Human perceptions and relation to boundary definition and demarcation are central elements of the theme to which I draw attention and include artistic creation. The analyses show how Ekman constantly relates to tradition and renewal, to different literary direction and to other writers in her treatment of man as an image creator. Vargskinnet’s thematisation of borders in various forms highlights, above all, an ongoing struggle: the struggle for power over time and space. The importance of raising awareness of the driving forces behind our ideas of the world, of our place in it and of our relations with the outside world is also highlighted in these novels. Problematisations of artistic creation, boundaries and power struggle are also found in other novels by Ekman. Examples from two of these, Gör mig levande igen ( Make Me Alive Again), 1996 and Grand final i skojarbranschen (Grand Final in the Entertainment Industry), 2011, are therefore used to deepen the analyses of Vargskinnet’s border themes.The analytical starting points of the study are mainly derived from literary theory as well as philosophical and posthumanist, feminist theory. As time and space are important elements of Vargskinnet's border themes, Michail Bachtin’s theories of the chronotope — a concept referring to the artistic designs of time and space in novels — offer useful concepts and perspectives. These make it possible to distinguish patterns in the novel’s text, in the form of repetitions and variations. Some constellations of images and descriptions recur.Maurice Merleau-Ponty’s phenomenological philosophy deals with human perceptions of the relationship between form and content, as well as various border phenomena, mainly based on the body and our senses. Verbal images are particularly important in his philosophy and this applies not least to innovative metaphors. These are most prominent in his late writings, such as the posthumously published The Visible and the Invisible (1968). The complex relationship between inner and outer, as well as the creative potential of image creation, are important motives in Vargskinnet and Merleau-Ponty’s concepts and reasoning highlight their function in the trilogy.Rosi Braidotti is associated with both material feminism and posthumanism and is today one of the leading theorists in these fields of research. Braidotti’s intriguing interdisciplinary perspectives and the breadth of the range of questions she discusses make her theories difficult to summarise, but something I have taken on in the study of Vargskinnet is her quest for a new, non-linear way in which to describe and understand the world. On the one hand, it can be said to be characteristic of Ekman’s style, and on the other hand it fits well into my search for patterns in the form of recurring border motifs in her novels.
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| 5. |
- Lindell, Lina, 1977-, et al.
(författare)
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Journey to the destination: a circular tourism economy : a training program for the hospitality industry to facilitate a transition towards increased circularity in the South Baltic Region
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Being aware of the extent of the tourism industry and that it is ever growing, which is also encouraged in many individual countries by the national and regional governments, it is evident that the tourism industry is an essential target group for introducing circular concepts and implementing circular solutions. Yet, this sector has so far received little attention in the literature and initiatives on circularity.Circular Economy (CE) goes beyond “green” or “environmental”, it includes all aspects of a community and challenges us to create solutions that are completely different from what we are used to. It also invites us to open up and interact with other stakeholders and the general public.In your hands is the first training material in circular economy specifically developed for small to medium sized companies of the tourism industry in the South Baltic Region. It is a small but important step in the direction towards circularity and a wellbeing society. Through this work we have shown that despite cultural challenges and regional differences there is a shared, common interest in making tourism more sustainable and even to work together towards a transformation of the hospitality industry. This common vision has been stronger than the challenges we faced in making this work and this is what will ensure the continued growing awareness on circularity and its integration in different sectors in our communities. In this work we have featured some of the groundbreaking experts in this field, and some of the first good practices from our regions. They are all courageous pioneers in a field that with time will become the norm. In fact, in the 10th Annual Forum of the EU strategy for the Baltic Sea Region (12-13/6/2019, Gdansk, Poland), CE was highlighted as the pathway to reach prosperity and wellbeing in the Baltic Sea Region.
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| 6. |
- Sandestig, Anna, et al.
(författare)
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Could Dissimilar Phenotypic Effects of ACTB Missense Mutations Reflect the Actin Conformational Change? : Two Novel Mutations and Literature Review
- 2018
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Ingår i: Molecular Syndromology. - : S. Karger. - 1661-8769 .- 1661-8777. ; 9:5, s. 259-265
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Tidskriftsartikel (refereegranskat)abstract
- The beta-actin gene encodes 1 of 6 different actin proteins. De novo heterozygous missense mutations in ACTB have been identified in patients with Baraitser-Winter syndrome (BRWS) and also in patients with developmental disorders other than BRWS, such as deafness, dystonia, and neutrophil dysfunction. We describe 2 different novel de novo missense ACTB mutations, c.208Camp;gt;G (p.Pro70Ala) and c.511Camp;gt;T (p.Leu171Phe), found by trio exome sequencing analysis of 2 unrelated patients: an 8-year-old boy with a suspected BRWS and a 4-year-old girl with unclear developmental disorder. The mutated residue in the first case is situated in the actin H-loop, which is involved in actin polymerization. The mutated residue in the second case (p.Leu171Phe) is found at the actin barbed end in the W-loop, important for binding to profilin and other actin-binding molecules. While the boy presented with a typical BRWS facial appearance, the girl showed facial features not recognizable as a BRWS gestalt as well as ventricular arrhythmia, cleft palate, thrombocytopenia, and gray matter heterotopia. We reviewed previously published ACTB missense mutations and ascertained that a number of them do not cause typical BRWS. By comparing clinical and molecular data, we speculate that the phenotypic differences found in ACTB missense mutation carriers might supposedly be dependent on the conformational change of ACTB.
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| 7. |
- Abrahamson, Josefin, et al.
(författare)
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Adolescent elite skiers with and without cam morphology did change their hip joint range of motion with 2 years follow-up
- 2019
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 27:10, s. 3149-3157
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate how range of motion of the hips and the lumbar spine are affected by continued elite, alpine skiing in young subjects, with and without a magnetic resonance imaging verified cam morphology, in a 2-year follow-up study. The hypothesis is that skiers with cam morphology will show a decrease in hip joint range of motion as compared with skiers without cam, after a 2-year follow-up. Method: Thirty adolescent elite alpine skiers were examined at the baseline (mean age 17.3 ± 0.7 years) and after 2 years. All skiers were examined for the presence of cam morphology (α-angle > 55°) using magnetic resonance imaging at the baseline. Clinical examinations of range of motion in standing lumbar flexion and extension, supine hip flexion, internal rotation, FABER test and sitting internal rotation and external rotation were performed both at the baseline and after 2 years. Results: Skiers with and without cam morphology showed a significant decrease from baseline to follow-up in both hips for supine internal rotation (right: mean − 13.3° and − 10.9° [P < 0.001]; left: mean − 7.6° [P = 0.004] and − 7.9° [P = 0.02]), sitting internal rotation (right: mean − 9.6° and − 6.3° [P < 0.001]; left: mean − 7.6° [P = 0.02] and − 3.3° [P = 0.008]) and sitting external rotation (right: mean − 16.9° and − 11.4° and left: mean − 17.9° and − 14.5° [P < 0.001]) and were shown to have an increased left hip flexion (mean + 8.4° and + 4.6° [P = 0.004]). Skiers with cam were also shown to have an increased right hip flexion (mean + 6.4° [P = 0.037]). Differences were found between cam and no-cam skiers from baseline to follow-up in the sitting internal rotation in both hips (right: mean 3.25°, left: mean 4.27° [P < 0.001]), the right hip flexion (mean 6.02° [P = 0.045]) and lumbar flexion (mean − 1.21°, [P = 0.009]). Conclusion: Young, elite alpine skiers with cam morphology decreased their internal rotation in sitting position as compared with skiers without the cam morphology after 2 years of continued elite skiing. Level of evidence: II.
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| 8. |
- Abrahamson, Josefin, et al.
(författare)
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Hip pain and its correlation with cam morphology in young skiers-a minimum of 5 years follow-up
- 2020
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Ingår i: Journal of Orthopaedic Surgery and Research. - : Springer Science and Business Media LLC. - 1749-799X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThere is conflicting evidence regarding the association between cam morphological changes and hip pain, and it remains unclear who with cam morphology will develop hip pain and who will not. This study aimed to investigate the correlation between cam morphology, hip pain, and activity level at a 5-year follow-up in young Alpine and Mogul skiers.MethodAll students (n = 76) at angstrom re Ski National Sports High School were invited and accepted participation in this prospective study at baseline. Magnetic resonance imaging (MRI) of both hips was conducted to evaluate the presence of cam morphology (alpha -angle >= 55 degrees) and its size alongside the reporting of hip pain, type, and frequency of training by the Back and hip questionnaire, at baseline. After 5 years, the skiers were invited to complete a shortened version of the same questionnaire.ResultsA total of 60 skiers (80%) completed the follow-up questionnaire, of which 53 had concomitant MRI data. Cam morphology was present in 25 skiers (47.2%, 39 hips). Hip pain at baseline and at follow-up was reported in 17 (28.3%) and 22 (36.7%) skiers, respectively. No correlations were found between the activity level, the frequency, and the size of cam morphology and hip pain, except for the right hip alpha -angle at 1 o'clock and hip pain in skiers with cam morphology at baseline (r(s) = 0.49; P = 0.03) and at follow-up (r(s) = 0.47; P = 0.04). A total of 73.3% skiers had retired, of which 48% reported this was due to injuries.ConclusionHip pain was not shown to be correlated, or had a low correlation, with activity level and the presence and size of cam morphology in young skiers on a 5-year follow-up. Based on these results, cam morphology or activity level did not affect hip pain to develop during 5 years of follow-up in young skiers. Furthermore, this study highlights that almost 75% of young elite skiers had retired from their elite career with almost 50% reporting that this was due to injuries sustained from skiing.
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| 9. |
- Adolfsson, Emma, 1977-, et al.
(författare)
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Technical in-depth comparison of two massive parallel DNA-sequencing methods for formalin-fixed paraffin-embedded tissue from victims of sudden cardiac death
- 2021
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 53
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Tidskriftsartikel (refereegranskat)abstract
- Sudden cardiac death (SCD) is a tragic and traumatic event. SCD is often associated with hereditary genetic disease and in such cases, sequencing of stored formalin fixed paraffin embedded (FFPE) tissue is often crucial in trying to find a causal genetic variant. This study was designed to compare two massive parallel sequencing assays for differences in sensitivity and precision regarding variants related to SCD in FFPE material. From eight cases of SCD where DNA from blood had been sequenced using HaloPlex, corresponding FFPE samples were collected six years later. DNA from FFPE samples were amplified using HaloPlex HS, sequenced on MiSeq, representing the first method, as well as amplified using modified Twist and sequenced on NextSeq, representing the second method. Molecular barcodes were included to distinguish artefacts from true variants. In both approaches, read coverage, uniformity and variant detection were compared using genomic DNA isolated from blood and corresponding FFPE tissue, respectively. In terms of coverage uniformity, Twist performed better than HaloPlex HS for FFPE samples. Despite higher overall coverage, amplicon-based HaloPlex technologies, both for blood and FFPE tissue, suffered from design and/or performance issues resulting in genes lacking complete coverage. Although Twist had considerably lower overall mean coverage, high uniformity resulted in equal or higher fraction of genes covered at ≥ 20X. By comparing variants found in the matched samples in a pre-defined cardiodiagnostic gene panel, HaloPlex HS for FFPE material resulted in high sensitivity, 98.0% (range 96.6-100%), and high precision, 99.9% (range 99.5-100%) for moderately fragmented samples, but suffered from reduced sensitivity (range 74.2-91.1%) in more severely fragmented samples due to lack of coverage. Twist had high sensitivity, 97.8% (range 96.8-98.7%) and high precision, 99.9% (range 99.3-100%) in all analyzed samples, including the severely fragmented samples.
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| 10. |
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